Abstract 56P
Background
Lung adenocarcinoma is a complex and heterogeneous disease characterized by diverse molecular alterations. Programmed death-ligand 1 (PD-L1) expression is a crucial biomarker in treatment algorithms, yet its clinico-pathological correlations with other mutations remain unclear. This study aims to investigate the impact of PD-L1 expression on outcomes in patients with KRAS mutations.
Methods
A single-center retrospective cohort study included patients diagnosed with non-squamous NSCLC between January 2018 and July 2022. A targeted next-generation sequencing (NGS) analysis by Ion Torrent® (ThermoFisher Scientific) (Ion AmpliSeq CLv2 panel) was performed. PD-L1 expression was assessed by Immunohistochemistry (ab SP263), and patients were categorized into PD-L1 <1% (negative), 1-49% (intermediate), and ≥ 50% (high).
Results
Clinical data from 464 patients were collected, revealing KRAS mutations in 179 patients (38.6%). 77 (43%) had a co-mutation, most frequently TP53 (74%) and STK11 (14.3%). Others co-mutations (24.7%) include MET, BRAF, FGFR2, SMAD4, ERBB4, PTEN, CTNNB1, PIK3CA, FBXW7. PD-L1 expression in KRAS mut cohort was negative in 59 (33,7%), intermediate in 61 (34.8%) and high in 55 pts (31,4%); in KRAS WildType: negative in 109 (39.9%), intermediate in 105 (38.4%) and high in 59 pts (21,6%); in patients with KRAS and a co-mutation was: negative in 22 (29%), intermediate in 22 (29%) and high in 33 pts (43,4%). Our data shows a higher incidence of PD-L1 expression in KRAS-mutated patients compared to KRAS wild-type (p=0.02), especially when presenting a co-mutation (p=0.003). Analysis of progression-free survival (PFS) after the first line of treatment with immune checkpoint inhibitors (ICIs) in 30 pts with stage IV KRAS-mutated NSCLC and high PD-L1 showed a trend favoring patients presenting a co-mutation (mPFS 13.7mo KRAS co-mutated vs. 3.6mo in KRAS only; HR 0.26; CI 95% 0.09-0.070; p=0.19).
Conclusions
These findings emphasize the importance of further exploring PD-L1 role in KRAS mutated patients, especially by taking into account accompanying mutations in other genes evaluated by NGS.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.